Hyperphenylalaninemia results from a variety of defects involving the multicomponent phenylalanine hydroxylase system. Using a number of applicable techniques which include an in vivo assessment of phenylalanine hydroxylase activity, the cofactor release assay, and measuring fibroblast reductase activity in affected patients, a clinic population of hyperphenylalaninemic patients will be examined to determine the effectiveness of these tests and the frequency of the occurrence of various defects.